The Notch receptors are cysteine-rich transmembrane polypeptides that are thought to mediate cell fate determination by acting as “gate keepers” that interpret environmental signals received by the cell. Depending on cell type and environmental context, activation of Notch may promote proliferation, differentiation, or even death. Activation of Notch cell-bound ligands (Delta and/or Jagged family members) results in the proteolytic cleavage of the intracellular domain of Notch (NICD) and its translocation to the cell nucleus, where it is recruited to target genes via interaction with RBP-Jκ, a DNA-binding component of the Notch pathway.